Correlation of Pain Reduction with fMRI BOLD Response in Osteoarthritis Patients Treated with Paracetamol: Randomized, Double-Blind, Crossover Clinical Efficacy Study

Abstract

ObjectiveTo assess the relationship between the analgesic efficacy of extended-release paracetamol (ER-APAP) and brain blood oxygen level–dependent (BOLD) signal activation in response to painful stimulation measured by functional magnetic resonance imaging (fMRI) in patients with osteoarthritis of the knee.MethodsThis placebo-controlled, double-blind, crossover, randomized trial (N = 25) comprised three treatment periods in which patients received four doses of an eight-hour ER-APAP caplet (2 x 665 mg), four doses of matched placebo, and no treatment. Pain intensity of the knee was measured before and after painful stimulation at the knee with osteoarthritis and before and after fMRI.ResultsER-APAP significantly reduced prestimulation osteoarthritis knee joint pain compared with baseline (P < 0.003) and placebo (P < 0.004). ER-APAP and placebo significantly reduced knee joint pain after stimulation (P = 0.014 and P = 0.032, respectively); however, pain reduction with ER-APAP was 35% greater than placebo. ER-APAP was associated with significant reductions in BOLD signal activation after stimulation compared with control in the sensory cortex (P = 0.002) and supramarginal gyrus (P = 0.003). Reduction in BOLD signal activation after stimulation for placebo was significantly greater than control in the subgenual prefrontal cortex (P < 0.001), frontal cortex (P < 0.001), insula (P < 0.003), and sensory cortex (P < 0.001).ConclusionsER-APAP had a significantly greater effect than placebo and no treatment in reducing knee pain, which was associated with reduced BOLD signal activations in pain pathways, including the sensory cortex and supramarginal gyrus. BOLD observations after placebo treatment may shed light on the role of the brain regions potentially involved in placebo response in clinical trials investigating pain therapies.

The neurologic pain signature responds to nonsteroidal anti-inflammatory treatment vs placebo in knee osteoarthritis

“…Previous literature provides robust evidence for acute knee pain-evoked activation in OA patients in regions overlapping with the NPS marker, including somatosensory cortices, insula, basal ganglia, thalamus, midbrain, anterior cingulate cortex, and amygdala. 9,33,59,62,71,90 As anticipated, the NPS showed good generalizability to this clinical population, to a different pain modality and when applied to a clinically affected site in 2 different OA patient samples. We observed a difference in absolute NPS scale between study 1 and study 2.…”

Mechanistic pain profiling as a tool to predict the efficacy of 3-week nonsteroidal anti-inflammatory drugs plus paracetamol in patients with painful knee osteoarthritis

“…Long-term use of NSAIDS may pose serious health risks [34] and hence tools for predicting the possible benefits are warranted. A recent study found that a reduction in the brain blood oxygen level-dependent signal activation of the sensory cortex and supramarginal gyrus in OA patients was associated with poor pain alleviation following treatment with paracetamol [60]. This indicates that measures of central sensitization could add prognostic information in treatment of OA.…”

Functional connectivity of the visual cortex differentiates anxiety comorbidity from episodic migraineurs without aura

“…According to the above mentioned studies, the abnormal visualrelated FC patterns may account for some clinical and psychiatric symptoms in MwoA patients, such as the frequency of headaches, cutaneous allodynia and anxiety comorbidity. Moreover, medication has shown the obvious influence of regulation on the core networks (DMN and CEN) and visual network [45,46]. Together with providing potential treatment strategies, these findings have revealed dysfunction in the integrity of migrainerelevant brain networks and may provide novel insights for the understanding of the mechanism and therapeutic strategies.…”